Literature DB >> 15146238

Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c.

Mitsuhiro Watanabe1, Sander M Houten, Li Wang, Antonio Moschetta, David J Mangelsdorf, Richard A Heyman, David D Moore, Johan Auwerx.   

Abstract

We explored the effects of bile acids on triglyceride (TG) homeostasis using a combination of molecular, cellular, and animal models. Cholic acid (CA) prevents hepatic TG accumulation, VLDL secretion, and elevated serum TG in mouse models of hypertriglyceridemia. At the molecular level, CA decreases hepatic expression of SREBP-1c and its lipogenic target genes. Through the use of mouse mutants for the short heterodimer partner (SHP) and liver X receptor (LXR) alpha and beta, we demonstrate the critical dependence of the reduction of SREBP-1c expression by either natural or synthetic farnesoid X receptor (FXR) agonists on both SHP and LXR alpha and LXR beta. These results suggest that strategies aimed at increasing FXR activity and the repressive effects of SHP should be explored to correct hypertriglyceridemia.

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Year:  2004        PMID： 15146238      PMCID： PMC406532          DOI： 10.1172/JCI21025

Source DB:  PubMed          Journal:  J Clin Invest        ISSN： 0021-9738            Impact factor:   14.808


  58 in total

1.  Identification of a chemical tool for the orphan nuclear receptor FXR.

Authors:  P R Maloney; D J Parks; C D Haffner; A M Fivush; G Chandra; K D Plunket; K L Creech; L B Moore; J G Wilson; M C Lewis; S A Jones; T M Willson
Journal:  J Med Chem       Date:  2000-08-10       Impact factor: 7.446

2.  Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta.

Authors:  J J Repa; G Liang; J Ou; Y Bashmakov; J M Lobaccaro; I Shimomura; B Shan; M S Brown; J L Goldstein; D J Mangelsdorf
Journal:  Genes Dev       Date:  2000-11-15       Impact factor: 11.361

3.  Role of LXRs in control of lipogenesis.

Authors:  J R Schultz; H Tu; A Luk; J J Repa; J C Medina; L Li; S Schwendner; S Wang; M Thoolen; D J Mangelsdorf; K D Lustig; B Shan
Journal:  Genes Dev       Date:  2000-11-15       Impact factor: 11.361

4.  The farnesoid X-activated receptor mediates bile acid activation of phospholipid transfer protein gene expression.

Authors:  N L Urizar; D H Dowhan; D D Moore
Journal:  J Biol Chem       Date:  2000-12-15       Impact factor: 5.157

5.  Diminished gene expression of ileal apical sodium bile acid transporter explains impaired absorption of bile acid in patients with hypertriglyceridemia.

Authors:  W C Duane; L A Hartich; A E Bartman; S B Ho
Journal:  J Lipid Res       Date:  2000-09       Impact factor: 5.922

6.  Dietary cholic acid lowers plasma levels of mouse and human apolipoprotein A-I primarily via a transcriptional mechanism.

Authors:  R A Srivastava; N Srivastava; M Averna
Journal:  Eur J Biochem       Date:  2000-07

7.  Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis.

Authors:  C J Sinal; M Tohkin; M Miyata; J M Ward; G Lambert; F J Gonzalez
Journal:  Cell       Date:  2000-09-15       Impact factor: 41.582

8.  A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis.

Authors:  B Goodwin; S A Jones; R R Price; M A Watson; D D McKee; L B Moore; C Galardi; J G Wilson; M C Lewis; M E Roth; P R Maloney; T M Willson; S A Kliewer
Journal:  Mol Cell       Date:  2000-09       Impact factor: 17.970

9.  Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors.

Authors:  T T Lu; M Makishima; J J Repa; K Schoonjans; T A Kerr; J Auwerx; D J Mangelsdorf
Journal:  Mol Cell       Date:  2000-09       Impact factor: 17.970

10.  Chenodeoxycholic acid and ursodeoxycholic acid effects in endogenous hypertriglyceridemias. A controlled double-blind trial.

Authors:  N Carulli; M Ponz de Leon; M Podda; M Zuin; A Strata; G Frigerio; A Digrisolo
Journal:  J Clin Pharmacol       Date:  1981-10       Impact factor: 3.126
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  411 in total

1.  Activation of the farnesoid X receptor induces hepatic expression and secretion of fibroblast growth factor 21.

Authors:  Holly A Cyphert; Xuemei Ge; Alison B Kohan; Lisa M Salati; Yanqiao Zhang; F Bradley Hillgartner
Journal:  J Biol Chem       Date:  2012-06-01       Impact factor: 5.157

2.  Lowering bile acid pool size with a synthetic farnesoid X receptor (FXR) agonist induces obesity and diabetes through reduced energy expenditure.

Authors:  Mitsuhiro Watanabe; Yasushi Horai; Sander M Houten; Kohkichi Morimoto; Taichi Sugizaki; Eri Arita; Chikage Mataki; Hiroyuki Sato; Yusuke Tanigawara; Kristina Schoonjans; Hiroshi Itoh; Johan Auwerx
Journal:  J Biol Chem       Date:  2011-06-01       Impact factor: 5.157

3.  Glucose and insulin induction of bile acid synthesis: mechanisms and implication in diabetes and obesity.

Authors:  Tiangang Li; Jessica M Francl; Shannon Boehme; Adrian Ochoa; Youcai Zhang; Curtis D Klaassen; Sandra K Erickson; John Y L Chiang
Journal:  J Biol Chem       Date:  2011-12-05       Impact factor: 5.157

4.  The effect of CYP7A1 polymorphisms on lipid responses to fenofibrate.

Authors:  Jian Shen; Donna K Arnett; Laurence D Parnell; Chao-Qiang Lai; Robert J Straka; Paul N Hopkins; Ping An; Mary F Feitosa; José M Ordovás
Journal:  J Cardiovasc Pharmacol       Date:  2012-03       Impact factor: 3.105

5.  Bile acid-induced inflammatory signaling in mice lacking Foxa2 in the liver leads to activation of mTOR and age-onset obesity.

Authors:  Irina Mikhailovna Bochkis; Soona Shin; Klaus Hermann Kaestner
Journal:  Mol Metab       Date:  2013-08-24       Impact factor: 7.422

6.  Activation of farnesoid X receptor prevents atherosclerotic lesion formation in LDLR-/- and apoE-/- mice.

Authors:  Helen B Hartman; Stephen J Gardell; Chris J Petucci; Shuguang Wang; Julie A Krueger; Mark J Evans
Journal:  J Lipid Res       Date:  2009-01-27       Impact factor: 5.922

7.  REV-ERBα Activates C/EBP Homologous Protein to Control Small Heterodimer Partner-Mediated Oscillation of Alcoholic Fatty Liver.

Authors:  Zhihong Yang; Hiroyuki Tsuchiya; Yuxia Zhang; Sangmin Lee; Chune Liu; Yi Huang; Gymar M Vargas; Li Wang
Journal:  Am J Pathol       Date:  2016-09-21       Impact factor: 4.307

8.  FXR activation by obeticholic acid or nonsteroidal agonists induces a human-like lipoprotein cholesterol change in mice with humanized chimeric liver.

Authors:  Romeo Papazyan; Xueqing Liu; Jingwen Liu; Bin Dong; Emily M Plummer; Ronald D Lewis; Jonathan D Roth; Mark A Young
Journal:  J Lipid Res       Date:  2018-03-20       Impact factor: 5.922

9.  Bile acid supplementation improves established liver steatosis in obese mice independently of glucagon-like peptide-1 secretion.

Authors:  Pablo Quintero; Margarita Pizarro; Nancy Solís; Juan Pablo Arab; Oslando Padilla; Arnoldo Riquelme; Marco Arrese
Journal:  J Physiol Biochem       Date:  2014-05-10       Impact factor: 4.158

10.  Farnesoid X receptor antagonizes JNK signaling pathway in liver carcinogenesis by activating SOD3.

Authors:  Yan-Dong Wang; Wei-Dong Chen; Cunbao Li; Cong Guo; Yanyan Li; Hui Qi; Hailing Shen; Jing Kong; Xuecheng Long; Frank Yuan; Xichun Wang; Wendong Huang
Journal:  Mol Endocrinol       Date:  2014-12-12
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